SPECIFIC AIMS OF THIS PROJECT: This project was originally designed to develop improved operative and nonoperative regimens that would improve the duration and quality of life in patients with cirrhosis. The primary objective in 1971 was in prospective, randomized fashion, using quantitative methodology, the physiologic and clinical response of patients with cirrhosis treated with transsplenic decompression (distal splenorenal shunt) procedure and classic portasystemic shunt. When, in 1976, it became apparent that the distal splenorenal shunt was significantly superior to classic portal decompression procedures, the prospective randomized study was discontinued and the emphasis of the study was shifted to the long-term follow-up of the study population. The specific aim of the project now is to continue to longitudinally follow this patient population and to study the basic science mechanisms altered by the pathophysiology of cirrhosis. During the last year and in years to come the emphasis of our studies will gradually shift to basic pathophysiology of cirrhosis. We anticipate that greater utilization of basic science methods will be required to answer clinical questions proposed by our study population. As in years past, the critical lack of a way of quantitating sinusoidal blood flow remains our primary unanswered question. The strength that we have developed to quantitatively study altered nitrogen metabolism will remain our primary model. In addition to continued study of nitrogen metabolism, the long-term follow-up and continued and expanding use of the LeVeen shunt in treating ascites in patients with cirrhosis needs further evaluation. In addition, the liver disease associated with jejunoileal bypass will continue to be studied.